Structural basis of the RNA-mediated Retron-Eco2 oligomerization.

IF 12.5 1区 生物学 Q1 CELL BIOLOGY
Yanjing Wang, Chen Wang, Yongqi Yin, Yongqing Cui, Zhikang Dai, Chang Liu, Yanke Chen, Zeyuan Guan, Tingting Zou
{"title":"Structural basis of the RNA-mediated Retron-Eco2 oligomerization.","authors":"Yanjing Wang, Chen Wang, Yongqi Yin, Yongqing Cui, Zhikang Dai, Chang Liu, Yanke Chen, Zeyuan Guan, Tingting Zou","doi":"10.1038/s41421-025-00823-y","DOIUrl":null,"url":null,"abstract":"<p><p>In the evolutionary arms race between bacteria and viruses, retrons have emerged as distinctive antiphage defense systems. Here, we elucidate the structure and function of Retron-Eco2, which comprises a non-coding RNA (ncRNA) that encodes multicopy single-stranded DNA (msDNA, a DNA‒RNA hybrid) and a fusion protein containing a reverse transcriptase (RT) domain and a topoisomerase-primase-like (Toprim) effector domain. The Eco2 msDNA and RT-Toprim fusion protein form a 1:1 stoichiometric nucleoprotein complex that further assembles into a trimer (msDNA:RT-Toprim ratio of 3:3) with a distinctive triangular configuration. The RNA portion of the msDNA in one protomer closely intertwines around the RT domain of an adjacent protomer, mediating the formation of this self-inhibitory assembly. Upon activation, the Toprim effector domain exhibits RNase activity, degrading RNA to arrest phage replication. We further reveal that phage mutants evading Eco2-mediated defense harbor mutations in the endonuclease IV-like protein DenB, underscoring DenB's critical role in triggering the activation of this system. Together, these findings provide key structural and functional insights into Retron-Eco2, laying the groundwork for harnessing its potential in biotechnology and synthetic biology applications.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"73"},"PeriodicalIF":12.5000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405507/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Discovery","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41421-025-00823-y","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

In the evolutionary arms race between bacteria and viruses, retrons have emerged as distinctive antiphage defense systems. Here, we elucidate the structure and function of Retron-Eco2, which comprises a non-coding RNA (ncRNA) that encodes multicopy single-stranded DNA (msDNA, a DNA‒RNA hybrid) and a fusion protein containing a reverse transcriptase (RT) domain and a topoisomerase-primase-like (Toprim) effector domain. The Eco2 msDNA and RT-Toprim fusion protein form a 1:1 stoichiometric nucleoprotein complex that further assembles into a trimer (msDNA:RT-Toprim ratio of 3:3) with a distinctive triangular configuration. The RNA portion of the msDNA in one protomer closely intertwines around the RT domain of an adjacent protomer, mediating the formation of this self-inhibitory assembly. Upon activation, the Toprim effector domain exhibits RNase activity, degrading RNA to arrest phage replication. We further reveal that phage mutants evading Eco2-mediated defense harbor mutations in the endonuclease IV-like protein DenB, underscoring DenB's critical role in triggering the activation of this system. Together, these findings provide key structural and functional insights into Retron-Eco2, laying the groundwork for harnessing its potential in biotechnology and synthetic biology applications.

rna介导的逆转录- eco2寡聚化的结构基础。
在细菌和病毒之间的进化军备竞赛中,逆转录酶作为独特的噬菌体防御系统出现。在这里,我们阐明了Retron-Eco2的结构和功能,它包括一个编码多拷贝单链DNA (msDNA, DNA - RNA杂交)的非编码RNA (ncRNA)和一个包含逆转录酶(RT)结构域和拓扑异构酶样引物(Toprim)效应域的融合蛋白。Eco2 msDNA和RT-Toprim融合蛋白形成1:1的化学计量核蛋白复合物,进一步组装成具有独特三角形结构的三聚体(msDNA:RT-Toprim比例为3:3)。一个原聚体中msDNA的RNA部分紧密缠绕在相邻原聚体的RT结构域周围,介导这种自抑制组装的形成。激活后,Toprim效应域表现出RNA酶活性,降解RNA以阻止噬菌体复制。我们进一步揭示了噬菌体突变体逃避eco2介导的防御,在内切酶iv样蛋白DenB中发生突变,强调了DenB在触发该系统激活中的关键作用。总之,这些发现提供了对Retron-Eco2的关键结构和功能的见解,为利用其在生物技术和合成生物学中的应用潜力奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Cell Discovery
Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍: Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信